Prevention of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation for assisted reproductive technologies (ART) MedDRA version: 8.1 Level: LLT Classification code 10021926 Term: Infertility
Conditions
Interventions
Trade Name: Orgalutran
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Ganirelix
Other descriptive name: GnRH Antagonist
Concentration unit: mg/ml milligram(s)/millilitre
Concentratio
Sponsors
Ferring Pharmaceuticals A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent Form, prior to screening evaluations 2. In good physical and mental health 3. Pre-menopausal females between the ages of 18-35 years (both inclusive) at the time of randomisation 4. Regular menstrual cycles of 26-35 days duration (both inclusive), presumed to be ovulatory 5. Body mass index (BMI) between 18 and 29 kg/m2 (both inclusive) 6. Transvaginal ultrasound documenting presence and adequate visualization of the uterus without obvious structural abnormalities which could compromise endometrial biopsy sampling (results obtained within 12 months prior to randomisation) 7. Transvaginal ultrasound documenting presence and adequate visualization of both ovaries, without evidence of abnormality (e.g., no endometrioma of 3 cm or greater), and normal adnexa (e.g., no hydrosalpinx) (results obtained within 6 months prior to randomisation) 8. Early follicular phase serum levels of FSH within normal limits (1-12 IU/L) (results obtained within 12 months prior to randomisation) 9. Early follicular phase antral follicle (2-10 mm) count = 10 on cycle day 3 (±1 d) of the screening cycle 10. Willing to donate the retrieved oocytes 11. Willing to use an adequate barrier method of contraception from informed consent to Day hCG injection +7 and to use an adequate barrier or hormonal method of contraception from Day hCG injection +7 to the end-of-study visit Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Abnormal karyotype 2. Any known clinically significant systemic disease (e.g., insulin dependent diabetes) 3. Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) which can compromise participation in the study 4. Diagnosed with polycystic ovarian syndrome or endometriosis stage III / IV 5. Diagnosed as “poor responder”, defined as a) > 20 days of gonadotrophin stimulation in a previous COH cycle, or b) Any previous cancellation of a COH cycle due to limited follicular response, or c) Development of less than 4 follicles = 15 mm in a previous COH cycle 6. History of recurrent miscarriage (defined as three consecutive spontaneous losses before weeks 24 of pregnancy) 7. Severe OHSS in a previous COH cycle 8. Undiagnosed vaginal bleeding 9. Pregnancy or lactation 10. Tumours of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus 11. Any concomitant medications that would interfere with evaluation of study medications. Specifically, any non-study hormonal therapy (except for thyroid medication), anti-psychotics (ATC code N05A), anti-depressants (ATC code N06), anxiolytics (ATC code N05B), hypnotics and sedatives (ATC code N05C) or continuous use of prostaglandin inhibitors (non-steroid anti-inflammatory drugs (NSAIDs), including aspirin) within 2 weeks prior to randomisation 12. Current or past (12 months prior to randomisation) abuse of alcohol or drugs, and/or current (last month) use of alcohol (more than 14 units per week) 13. Current or past (3 months prior to randomisation) smoking habit of more than 20 cigarettes per day 14. History of chemotherapy (except for gestational conditions) or radiotherapy 15. Use of any investigational drug during 3 months prior to start of the current COH cycle 16. Previous participation in the study 17. Hypersensitivity to any trial product
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the synchrony of the follicle cohort at the start of stimulation associated with a mid-luteal injection of degarelix compared to placebo • To describe the endometrial receptivity associated with the degarelix regimens (degarelix starting in the mid-luteal phase or degarelix starting in the early follicular phase) in comparison to the fixed gonadotrophin releasing hormone (GnRH) antagonist protocol, during controlled ovarian hyperstimulation with luteal support ;Secondary Objective: • To describe the ovarian / follicular development as well as the number of cumulus-oocyte complexes associated with the degarelix regimens in comparison to the fixed GnRH antagonist protocol • To describe the circulating concentrations of selected endocrine parameters during treatment with the degarelix regimens in comparison to the fixed GnRH antagonist protocol • To describe the treatment efficiency of the degarelix regimens in comparison to the fixed GnRH antagonist protocol • To explore the pharmacokinetics of degarelix • To establish the safety profile of the degarelix regimens in comparison to the fixed GnRH antagonist protocol ;Primary end point(s): • Coefficient of variation of follicular sizes on Stimulation Day 1 (follicles = 2 mm) • Frequency of oocyte donors with adequate secretory transformation at the endometrial histology evaluation on Day hCG injection +7 | — |
Countries
Belgium, Czech Republic, Spain
Outcome results
None listed